Tick-borne disease poses a significant threat to human and domestic animal health. The most common tick-borne disease in the United States is Lyme disease, which is caused by the spirochete bacteria Borrelia burgdorferi. The complex ecologic relationship between habitat, ticks, pathogens, and wildlife hosts has limited the effectiveness of previous vector control strategies. While no single control method has been shown to reduce tick abundance and associated pathogens, targeting multiple aspects of the tick/host/pathogen lifecycle with combinations of interventions may offer a more effective strategy. The purpose of this work is to investigate the impact of long-term integrated tick management on Ixodes scapularis (blacklegged ticks) and hosts in the Upper Midwest, as well as to investigate recombinant poxviruses as wildlife reservoir-targeted vaccine candidates against tick-borne diseases. To determine whether integration of two environmental control strategies is more effective compared to individual treatments at reducing host-seeking blacklegged tick densities, we conducted a five-year small-scale field trial in south central Wisconsin. The deployment of host-targeted acaricides (permethrin-treated cotton) reliably reduced nymph densities a year after deployment but the addition of habitat modification (invasive vegetation removal) did not improve outcomes. Permethrin-treated cotton impact was explained by reductions in tick and host contact. Overall, this treatment combination does not yield improved outcomes within this setting. Reservoir-targeted vaccination offers an intriguing approach to inhibiting tickborne disease transmission, especially in the case of Lyme disease. However, current strategies require repeated dosing in order to achieve protection. To address this concern, we evaluated highly attenuated poxvirus vectors as potential vaccine candidates. Orally administered, recombinant poxviruses induced robust, long-lasting antibody immune responses in Peromyscus leucopus (white-footed mice). With the insertion of multiple B. burgdorferi and I. scapularis genes as part of a multi-target vaccine approach, recombinant poxviruses induced high serum antibody titers with a protective borreliacidal profile in laboratory mice. These studies reveal the utility of recombinant poxviruses as multi-antigen vaccine vectors and provide considerations for future improvement.